Between 100,000 to 300,000 Americans die annually from pulmonary embolism (PE), which is more than breast cancer, AIDS, and traffic fatalities combined. PE is the 3rd leading cause of death in the United States. A similar incidence of PE is found in Europe with approximately 370,000 annual deaths. Moreover, PE is the third most common cause of death in trauma patients that survive the first 24 hours. An estimated 25% of all hospitalized patients have some form of deep vein thrombosis (DVT), which is often clinically unapparent unless PE develops. On average, 33% of DVT will progress to symptomatic PE, of which 10% will be fatal.
Risk factors for PE arising from DVT follow Virchow's Triad: (i) endothelial injury, (ii) hypercoaguability, and (iii) hemodynamic changes (stasis or turbulence). Specific at risk situations include hip and knee arthroplasty, abdominal, pelvic and extremity surgeries, pelvic and long bone fractures, major spine and brain trauma, prolonged immobility such as prolonged hospital stays and air travel, paralysis, advanced age, prior DVT, cancer, obesity, chronic obstructive pulmonary disease, diabetes, congestive heart failure, and other situations. Patients undergoing orthopedic procedures can carry a higher (e.g., 40-80%) risk for DVT and PE following knee and hip surgeries in the absence of prophylactic treatment, for example.
The American Academy of Orthopedic Surgeons (AAOS) has issued guidelines for PE prophylaxis. According to the AAOS, patients at standard risk of PE prophylaxis should be considered for chemoprophylactic agents such as aspirin, low molecular weight heparin (LMWH), synthetic pentassaccharides, or warfarin, in addition to intra-operative and/or immediate postoperative mechanical prophylaxis.
The duration of prophylaxis depends on the source of potential DVT. Current recommendations for prophylaxis comprise a minimum of seven to ten days for moderate to high risk surgeries and up to 28-35 days for many orthopedic surgeries. Studies indicate that hypercoaguability persists for at least one month after injury in about 80% of trauma patients. Overall, prophylactic treatment for possible venous thromboembolism (VTE), which is DVT and PE combined, is often warranted for up to 35 days following trauma or major surgery.
Contraindications for chemoprophylaxis include active bleeding, hemorrhagic diathesis, hemorrhagic stroke, neurologic surgery, extensive trauma, hemothorax, pelvic or lower extremity fractures with intracranial bleeding, and anticoagulation interruption.
For patients who are contraindicated for the above-mentioned anti-coagulation prophylaxis, or where anti-coagulation therapy has failed, the Society of Interventional Radiology, AAOS, American College of Physicians, and the British Committee of Standards in Haematology recommend the use of venous filters. These intravascular blood filters are typically deployed via catheter into the inferior vena cava (IVC) to catch emboli arising from lower extremity DVT before reaching the heart or pulmonary arterial circulation. Furthermore, the British Committee of Standards in Hematology recommends IVC filter placement in pregnant patients who have contraindications to anticoagulation and develop extensive VTE shortly before delivery (e.g., within 2 weeks).
The Eastern Association for Surgery of Trauma further recommends prophylactic IVC filters placed in trauma patients who are at increased risk of bleeding and prolonged immobilization. Such prophylactic recommendation follows studies that demonstrate a low rate of PE in patients with severe polytrauma who underwent IVC filter placement. A systematic study on the effectiveness of prophylactic IVC filters in trauma patients revealed a consistent reduction in PE with a relative risk of 0.20. Hence, in controlled clinical studies, trauma patients are about five times more likely to have a PE without an IVC filter. Moreover, analysis has revealed that no fatal PEs occurred in the IVC filter arms of any of the included studies, yet 20 fatal PEs occurred in the 407 patients not receiving IVC filters.
Many IVC filters installed were expected to be permanent fixtures since endothelialization usually occurs within 7-10 days, making some models impractical to remove without irreversible vascular damage, potentially leading to life threatening bleeding, dissection of the IVC, and/or thrombosis. Although these permanent filters have prevented PE, they have been shown to actually increase the risk of recurrent DVT over time. For example, in one randomized controlled trial the incidence of DVT within the IVC filter cohort increased almost two times: (i) a 21% incidence of recurrent DVT in the filter cohort vs. 12% in the non-filter cohort at 2 years (p=0.02), and (ii) a 36% incidence of recurrent DVT in the filter cohort versus 15% in the non-filter group at 8 years (p=0.042). The filters did reduce the occurrence of PE. The filter cohort experienced only 1% PE versus the non-filter cohort posting 5% PE in the first 12 days (p=0.03). Apparently the initial benefit of reduced PE with permanent IVC filters is offset by an increase in DVT.
In addition to increased incidence of DVT for prolonged IVC filter deployment, filter occlusion has been reported with some models at about a 6% to 30% occurrence, as well as filter migration (about a 3% to 69% occurrence), venous insufficiency (about a 5% to 59% occurrence), and post thrombotic syndrome (about a 13% to 41% occurrence). Complications from insertion including hematoma, infection, pneumothorax, stroke, air embolism, misplacement, device migration, vein perforation, arteriovenous fistula, and inadvertent carotid artery puncture have an occurrence rate of about 4%-11%.
Retrievable IVC filters have been marketed more recently. Retrievable IVC filters are intended to be removed when the indication has expired, and hence circumvent many of the deleterious complications of permanent filters such as increased risk of DVT. The retrievable filters feature flexible hooks, collapsing components, fewer barbed struts, unrestrained legs, and/or other features to ease retrieval. Unfortunately, many of these same features have led to unwanted side effects, including filter migration, fatigue failure leading to fracture, IVC penetration, fragment migration to hepatic veins and pulmonary arteries, filter tilt, and metallic emboli, for example. In a recent study perforation of the IVC by leading retrievable IVC filters was shown to be the rule, not the exception, as about 86% of the filters on computed tomography (CT) scans obtained between 1 and 880 days after filter placement had perforated the IVC. These adverse events prompted the Food and Drug Administration (FDA) to issue a formal communication stating that “FDA recommends that implanting physicians and clinicians responsible for the ongoing care of patients with retrievable IVC filters consider removing the filter as soon as protection from PE is no longer needed.” Moreover, in 2014, a second communication released by the FDA recommended that retrievable IVC filters be removed between 29 and 54 days after deployment for patients in whom the transient risk of PE has passed. Even though these types of retrievable filters are often intended to be removed within approximately 3 months, at which time the technical retrieval success rate is 94% (versus 37% at 12 months), several studies indicate that approximately 70%-80% of patients with retrievable filters do not return to the hospital for subsequent filter retrieval.
Due to the mounting complications of metallic retrievable IVC filters following extended indwelling times, combined with the reluctance of patients to return for IVC filter retrieval, fully absorbable IVC filters have been proposed that obviate retrieval by simply breaking down into carbon dioxide and water and/or other materials several months following the risk period for PE. Furthermore, these absorbable IVC filters are much more flexible than conventional metal IVC filters rendering them less capable of perforating the IVC and impaling neighboring organs.